The mechanisms of recovery and rehabilitation of motor function following stroke are poorly understood. Functional imaging using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) points to the potential role of intact brain regions in both the stroke and non-stroke cerebral hemispheres. However, the mechanisms of post-stroke reCOvery were not identified in these studies, in part because of methodological problems that include limitations of PET and fMRI, small sample sizes, selection of patients with good recovery, and failure to control for bilateral movements during imaging of putatively unilateral motor tasks. Nevertheless, results of these studies point to specific hypotheses that need to be addressed in a larger study with adequate controls. There is also a need to investigate mechanisms mediating the beneficial effects of physical rehabilitation. We will use magnetoencephalography (MEG) to investigate the neurologic mechanisms of recovery from hemiparesis in 75 adults during recovery from a first-ever, unilateral cerebral infarction. Recovery will be measured behaviorally using upper-extremity (UE) motor performance tasks, including grip strength and peg-placing, and ratings of daily living activities. Using MEG, brain activation will be recorded during instructed movements of the affected and unaffected UEs. MEG and motor performance studies will be performed longitudinally at 2-3 and 10-12 months post-stroke in order to investigate relationships between recovery of motor performance and evolution of brain activation maps. During MEG imaging, movements of both UEs will be monitored using electromyography (EMG) in order to determine if uninstructed movements of the unaffected UE occur during instructed movements of the affected UE and if these uninstructed movements are the cause of observed activation in the non-stroke hemisphere. We will investigate differences between the stroke and non-stroke hemispheres in the latency and amplitude of evoked field (EF) peaks and the topography of brain activation profiles during voluntary movements of the contralateral UE. We will also investigate how the size and location of the stroke lesion (volumetrically determined on the basis of structural MR scans) influence motor activation maps and their evolution during the year post-stroke. tn a subsidiary study, we will investigate how physical rehabilitation influences cortical motor reorganization by performing MEG motor activation studies of 24 adult subacute stroke patients who completed a randomized, controlled clinical trial, conducted by Dr. James Grotta at University of Texas-Houston, comparing 12 patients who receive constraint-induced movement therapy (CIMT) for 3 hours per day with 12 control patients who receive traditional physical and occupational therapy at the same intensity.